The long-term goal of this project is to define the biochemical mechanisms that cause embryonic cells to adopt particular fates as a function of their position in the embryo. In the Drosophila embryo, the polarity and basic features of the dorsal-ventral pattern are controlled by the products of 11 maternally-expressed genes. The biochemical activities of these products will be studied. Experiments will focus on biochemical and molecular characterization of the Toll gene product, which plays a central role in defining dorsal-ventral polarity. Based on its sequence, the Toll gene appears to encode a transmembrane protein. Since the activity of the Toll protein appears to be directly reflected in cell fate, the sequence suggests that studies of the Toll protein will define how the activity of a membrane protein directs cell determination. Proposed experiments will test whether the Toll protein is associated with membranes and, if so, which membranes in the embryo contain the Toll protein. Mutant Toll alleles with a variety of profound effects on embryonic pattern will be sequenced to define sites in the protein that are important for its activity and the regulation of its activity. A pathway of interactions among the maternal products will be worked out by biochemical and genetic identification of products that interact with the Toll protein. The easter gene, which is also crucial for the embryonic dorsal-ventral pattern, will be sequenced, its protein localized in the embryo, and the possible interaction of the easter product with the Toll protein characterized. Other maternal and zygotic components of the process of dorsal-ventral pattern formation will be cloned by transposon tagging, and their DNA sequenced to help define their roles in pattern formation.